Skip to main content

Advertisement

Log in

Inhibition of C3a/C3aR Axis in Diverse Stages of Ulcerative Colitis Affected the Prognosis of UC by Modulating the Pyroptosis and Expression of Caspase-11

  • Original Article
  • Published:
Inflammation Aims and scope Submit manuscript

A Correction to this article was published on 10 November 2020

This article has been updated

Abstract

Ulcerative colitis (UC) is a serious digestive system disease. Furthermore, the activation of C3a/C3aR axis promoted the expression of caspase-11. And higher levels of caspase-11 could induce the pyroptosis and inflammation of cells. However, some studies suggested that caspase-11 could promote and suppress the inflammation during the development of UC. In addition, whether C3a/C3aR axis could affect the development of UC by modulating the expression of caspase-11 is unclear. We established the UC rat model in this study. Next, the C3aR inhibitor was used to treat these rats at diverse stages of UC. Next, the HE staining was performed to detect the intestinal damage. ELISA was performed to reveal the expression of IL-6 and TNF-α in different stages of UC. Western blotting was used to detect the expression of caspase-11 and C3aR in different stages of UC. Stimulation of C3aR inhibitor in early stage of UC promoted the expression of C3aR and caspase-11 in later stage of UC. Treatment of C3aR inhibitor in later stage of UC inhibited the expression of C3aR and caspase-11 in later stage of UC. Furthermore, application of C3aR inhibitor in early stage of UC aggravates the damage of colon tissue and enhanced the secretion of TNF-α and IL-6 in the later stage of UC. Treatment of C3aR inhibitor in later stage of UC relieved the symptoms of UC and suppressed the production of TNF-α and IL-6 in the later stage of UC. Application of C3aR inhibitor in early stage of UC induced the poor prognosis of UC by upregulating the expression of caspase-11. Treatment of C3aR inhibitor in later stage of UC relieved the symptoms of UC and lead to the favorable prognosis of UC by inhibiting the expression of caspase-11.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Change history

  • 10 November 2020

    Following publication of our article [1], we noticed an error in Fig. 1.

References

  1. Feuerstein, J.D., A.C. Moss, and F.A. Farraye. 2019. Ulcerative colitis. Mayo Clinic Proceedings 94: 1357–1373.

    Article  Google Scholar 

  2. Sun, P.L., and S. Zhang. 2018. Correlations of 25-hydroxyvitamin D3 level in patients with ulcerative colitis with inflammation level, immunity and disease activity. European Review for Medical and Pharmacological Sciences 22: 5635–5639.

    PubMed  Google Scholar 

  3. Zhang, Y., Z. Wang, J. Liu, S. Zhang, J. Fei, J. Li, T. Zhang, J. Wang, P.W. Park, and Y. Chen. 2017. Cell surface-anchored syndecan-1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis. Journal of Cellular and Molecular Medicine 21: 13–25.

    Article  CAS  Google Scholar 

  4. Lacey, C.A., W.J. Mitchell, A.S. Dadelahi, and J.A. Skyberg. 2018. Caspase-1 and caspase-11 mediate pyroptosis, inflammation, and control of brucella joint infection. Infection and Immunity 86(9): e00361–18.

  5. Ding, J., K. Wang, W. Liu, Y. She, Q. Sun, J. Shi, H. Sun, D.C. Wang, and F. Shao. 2016. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535: 111–116.

    Article  CAS  Google Scholar 

  6. Kayagaki, N., S. Warming, M. Lamkanfi, L. Vande Walle, S. Louie, J. Dong, K. Newton, Y. Qu, J. Liu, S. Heldens, J. Zhang, W.P. Lee, M. Roose-Girma, and V.M. Dixit. 2011. Non-canonical inflammasome activation targets caspase-11. Nature 479: 117–121.

    Article  CAS  Google Scholar 

  7. Sborgi, L., S. Rühl, E. Mulvihill, J. Pipercevic, R. Heilig, H. Stahlberg, C.J. Farady, D.J. Müller, P. Broz, and S. Hiller. 2016. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. The EMBO Journal 35: 1766–1778.

    Article  CAS  Google Scholar 

  8. Pandolfi, F., S. Altamura, S. Frosali, and P. Conti. 2016. Key role of DAMP in inflammation, cancer, and tissue repair. Clinical Therapeutics 38: 1017–1028.

    Article  CAS  Google Scholar 

  9. Napier, B.A., S.W. Brubaker, T.E. Sweeney, P. Monette, G.H. Rothmeier, N.A. Gertsvolf, A. Puschnik, J.E. Carette, P. Khatri, and D.M. Monack. 2016. Complement pathway amplifies caspase-11-dependent cell death and endotoxin-induced sepsis severity. The Journal of Experimental Medicine 213: 2365–2382.

    Article  CAS  Google Scholar 

  10. Ye, J., Z. Qian, M. Xue, Y. Liu, S. Zhu, Y. Li, X. Liu, D. Cai, J. Rui, and L. Zhang. 2019. Aristolochic acid I aggravates renal injury by activating the C3a/C3aR complement system. Toxicology Letters 312: 118–124.

    Article  CAS  Google Scholar 

  11. Li, Y., Z. Yang, M. Chavko, B. Liu, O.A. Aderemi, M.O. Simovic, M.A. Dubick, and L.C. Cancio. 2018. Complement inhibition ameliorates blast-induced acute lung injury in rats: potential role of complement in intracellular HMGB1-mediated inflammation. PLoS ONE 13: e0202594.

    Article  Google Scholar 

  12. Demon, D., A. Kuchmiy, A. Fossoul, Q. Zhu, T.D. Kanneganti, and M. Lamkanfi. 2014. Caspase-11 is expressed in the colonic mucosa and protects against dextran sodium sulfate-induced colitis. Mucosal Immunology 7: 1480–1491.

    Article  CAS  Google Scholar 

  13. Hsu, J.L., J.W. Chou, T.F. Chen, J.T. Hsu, F.Y. Su, J.L. Lan, P.C. Wu, C.M. Hu, E.Y. Lee, and W.H. Lee. 2020. Glutathione peroxidase 8 negatively regulates caspase-4/11 to protect against colitis. EMBO Molecular Medicine 12: e9386.

    Article  CAS  Google Scholar 

  14. Márquez-Flores, Y.K., I. Villegas, A. Cárdeno, M. Rosillo, and C. Alarcón-de-la-Lastra. 2016. Apigenin supplementation protects the development of dextran sulfate sodium-induced murine experimental colitis by inhibiting canonical and non-canonical inflammasome signaling pathways. The Journal of Nutritional Biochemistry 30: 143–152.

    Article  Google Scholar 

  15. Walujkar, S.A., S.V. Kumbhare, N.P. Marathe, D.V. Patangia, P.S. Lawate, R.S. Bharadwaj, and Y.S. Shouche. 2018. Molecular profiling of mucosal tissue associated microbiota in patients manifesting acute exacerbations and remission stage of ulcerative colitis. World Journal of Microbiology and Biotechnology 34: 76.

    Article  Google Scholar 

  16. Feuerstein, J.D., and A.S. Cheifetz. 2014. Ulcerative colitis: epidemiology, diagnosis, and management. Mayo Clinic Proceedings 89: 1553–1563.

    Article  Google Scholar 

  17. Ordás, I., L. Eckmann, M. Talamini, D.C. Baumgart, and W.J. Sandborn. 2012. Ulcerative colitis. The Lancet (London, England) 380: 1606–1619.

    Article  Google Scholar 

  18. Clemson, C.M., J.N. Hutchinson, S.A. Sara, A.W. Ensminger, A.H. Fox, A. Chess, and J.B. Lawrence. 2009. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Molecular Cell 33: 717–726.

    Article  CAS  Google Scholar 

  19. Tatiya-Aphiradee, N., W. Chatuphonprasert, and K. Jarukamjorn. 2018. Immune response and inflammatory pathway of ulcerative colitis. Journal of Basic and Clinical Physiology and Pharmacology 30: 1–10.

    Article  Google Scholar 

  20. Kubes, P., and C. Jenne. 2018. Immune responses in the liver. Annual Review of Immunology 36: 247–277.

    Article  CAS  Google Scholar 

  21. Lubbers, R., M.F. van Essen, C. van Kooten, and L.A. Trouw. 2017. Production of complement components by cells of the immune system. Clinical and Experimental Immunology 188: 183–194.

    Article  CAS  Google Scholar 

  22. Shang, J., W. Liu, C. Yin, H. Chu, and M. Zhang. 2019. Cucurbitacin E ameliorates lipopolysaccharide-evoked injury, inflammation and MUC5AC expression in bronchial epithelial cells by restraining the HMGB1-TLR4-NF-κB signaling. Molecular Immunology 114: 571–577.

    Article  CAS  Google Scholar 

  23. Ye, Z., L. Zhang, R. Li, W. Dong, S. Liu, Z. Li, H. Liang, L. Wang, W. Shi, A.B. Malik, K.T. Cheng, and X. Liang. 2019. Caspase-11 mediates Pyroptosis of tubular epithelial cells and septic acute kidney injury. Kidney & Blood Pressure Research 44: 465–478.

    Article  CAS  Google Scholar 

  24. Zhang, Z., X. Shao, N. Jiang, S. Mou, L. Gu, S. Li, Q. Lin, Y. He, M. Zhang, W. Zhou, and Z. Ni. 2018. Caspase-11-mediated tubular epithelial pyroptosis underlies contrast-induced acute kidney injury. Cell Death & Disease 9: 983.

    Article  Google Scholar 

  25. Lei, Q., T. Yi, and C. Chen. 2018. NF-κB-Gasdermin D (GSDMD) axis couples oxidative stress and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome-mediated cardiomyocyte pyroptosis following myocardial infarction. Medical Science Monitor : international medical journal of experimental and clinical research 24: 6044–6052.

    Article  CAS  Google Scholar 

  26. Liu, Z., L. Gan, Y. Xu, D. Luo, Q. Ren, S. Wu, and C. Sun. 2017. Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue. Journal of Pineal Research 63(1).

  27. Gu, P., L. Zhu, Y. Liu, L. Zhang, J. Liu, and H. Shen. 2017. Protective effects of paeoniflorin on TNBS-induced ulcerative colitis through inhibiting NF-kappaB pathway and apoptosis in mice. International Immunopharmacology 50: 152–160.

    Article  CAS  Google Scholar 

  28. Shen, J., J. Cheng, S. Zhu, J. Zhao, Q. Ye, Y. Xu, H. Dong, and X. Zheng. 2019. Regulating effect of baicalin on IKK/IKB/NF-kB signaling pathway and apoptosis-related proteins in rats with ulcerative colitis. International Immunopharmacology 73: 193–200.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wenmin Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, X., Chen, Y., Yu, S. et al. Inhibition of C3a/C3aR Axis in Diverse Stages of Ulcerative Colitis Affected the Prognosis of UC by Modulating the Pyroptosis and Expression of Caspase-11. Inflammation 43, 2128–2136 (2020). https://doi.org/10.1007/s10753-020-01280-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-020-01280-3

KEY WORDS

Navigation